A sensitive assay for the quantification of morphine and its active metabolites in human plasma and dried blood spots using high-performance liquid chromatography–tandem mass spectrometry

Clavijo, Claudia F.; Hoffman, Keith L.; Thomas, James J.; Carvalho, Brendan; Chu, Larry F.; Drover, David R.; Hammer, Gregory B.; Christians, Uwe; Galinkin, Jeffrey L.

doi:10.1007/s00216-011-4775-z

Cited by 69 publications

(57 citation statements)

References 22 publications

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“…Morphine, M3G, and M6G were simultaneously measured in plasma using a validated liquid chromatography tandem mass spectrometry assay previously developed by our group (21). The assay had the following performance characteristics: range of reliable response of 0.25-1,000 ng/ mL (r 2 >0.99) for morphine, 1-1,000 ng/mL (r 2 >0.99) for M3G, and 2.5-1,000 ng/mL (r 2 >0.99) for M6G.…”

Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery

Elkomy

Drover

Glotzbach

et al. 2015

AAPS J

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ABSTRACT. The objective of this study was to characterize morphine glucuronidation in infants and children following cardiac surgery for possible treatment individualization in this population. Twenty children aged 3 days to 6 years, admitted to the cardiovascular intensive care unit after congenital heart surgery, received an intravenous (IV) loading dose of morphine (0.15 mg/kg) followed by subsequent intermittent IV bolus doses based on a validated pain scale. Plasma samples were collected over 6 h after the loading dose and randomly after follow-up doses to measure morphine and its major metabolite concentrations. A population pharmacokinetic model was developed with the non-linear mixed effects software NONMEM. Parent disposition was adequately described by a linear two-compartment model. Effect of growth (size and maturation) on morphine parameters was accounted for by allometric body weight-based models. An intermediate compartment with Emax model best characterized glucuronide concentrations. Glomerular filtration rate was identified as a significant predictor of glucuronide formation time delay and maximum concentrations. Clearance of morphine in children with congenital heart disease is comparable to that reported in children without cardiac abnormalities of similar age. Children 1-6 months of age need higher morphine doses per kilogram to achieve an area under concentration-time curve comparable to that in older children. Pediatric patients with renal failure receiving morphine therapy are at increased risk of developing opioid toxicity due to accumulation of morphine metabolites.

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Section: Methodsmentioning

confidence: 99%

Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery

Elkomy

Drover

Glotzbach

et al. 2015

AAPS J

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“…Ghassabian et al simultaneously analyzed morphine, fentanyl, midazolam, and their major metabolites in human blood using LC-MS/MS [25], with the linear concentration ranges from 3.5 to 700 ng/mL for morphine and its metabolites. Clavijo et al determined morphine and its active metabolites M3G and M6G in human plasma and dried blood spots with a linear range of 0.25-100 ng/mL for morphine and M3G, and 1ß100 ng/mL for M6G [26]. Andersson et al detected the ratio of M3S/M3G and M6S/M6G in human plasma and urine using M6G-d3 deuterated as IS to make a relative quantification, but the retention time for determining morphine, M3S/M6S, M3G/M6G, and IS was as long as 2.4 min [27].…”

Section: Discussionmentioning

confidence: 99%

Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid‐phase extraction with ultra‐high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard

Yang

Wang

et al. 2016

J of Separation Science

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Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid-phase extraction with ultra-high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard A rapid and sensitive bioassay was established and validated to simultaneously determine gemfibrozil, morphine, morphine-3␤-glucuronide, and morphine-6␤-glucuronide in mouse cerebrum, epencephalon, and hippocampus based on ultra-high performance liquid chromatography and tandem mass spectrometry. The deuterated internal standard, M6G-d3, was mixed with the prepared samples at 10 ng/mL as the final concentration. The samples were transferred into the C 18 solid-phase extraction columns with gradient elution for solid-phase extraction. The mobile phase consisted of methanol and 0.05% formic acid (pH 3. and M6G with correlation coefficients >0.993. The lower limit of quantitation for all four analytes was 0.05 ng/mL, relative standard deviation of intra-and interday precision was less than 10.5%, and the relative error of accuracy was from −8.2 to 8.3% at low, medium, and high concentrations for all the analytes. In conclusion, gemfibrozil can influence the morphine antinociception after coronary heart disease induced chronic angina by the change in one of morphine metabolites', M3G, distribution in mouse brain.

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“…In general, surface modification can be accomplished by physical and/or chemical adsorption of the desired molecules to coat the surface, depending on the specific applications [22]. Many analytical methods have been developed for the determination of morphine, including gas chromatography (GC) [23], high performance liquid chromatography (HPLC) [24], capillary electrophoresis [25], chemiluminescence [26], spectrophotometry [27], ion mobility spectrometry [28,29], surface plasma resonance (SPR) [30] and electrochemical methods [31][32][33][34][35][36][37][38]. Among them, chromatographic methods are most commonly used for the determination of trace morphine [39].…”

Section: Introductionmentioning

confidence: 99%

Silane modified magnetic nanoparticles as a novel adsorbent for determination of morphine at trace levels in human hair samples by high-performance liquid chromatography with diode array detection

Boojaria

Masrournia

Ghorbani

et al. 2015

Forensic Sci Med Pathol

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In this paper we report a novel, sensitive, and rapid method of magnetic solid phase extraction based on surface modified magnetic nanoparticles as a novel nano sorbent for HPLC determination of morphine with diode array detection in human hair samples. Factors affecting the extraction efficiency of the proposed method, including the sample pH, quantity of magnetic nanoparticles, sample volume, desorption solvent type and its volume, and extraction time were investigated and optimized. Under the optimized experimental conditions, a good linearity was observed in the range of 1-800 µgL(-1) for the morphine, with a correlation coefficient (R (2)) of 0.990. The pre-concentration factor of 208.69 was achieved in this method. The detection limit of the method was 0.1 μgL(-1) based on S/N = 3 and good reproducibility with a relative standard deviations lower than (n = 5) 2.59 %. The proposed method has been successfully applied to the analysis of trace amounts of morphine in human hair samples with satisfactory results. This method can be applied in medical toxicology research and forensic medical centers.

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A sensitive assay for the quantification of morphine and its active metabolites in human plasma and dried blood spots using high-performance liquid chromatography–tandem mass spectrometry

Cited by 69 publications

References 22 publications

Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery

Pharmacokinetics of Morphine and Its Metabolites in Infants and Young Children After Congenital Heart Surgery

Simultaneous analysis of gemfibrozil, morphine, and its two active metabolites in different mouse brain structures using solid‐phase extraction with ultra‐high performance liquid chromatography and tandem mass spectrometry with a deuterated internal standard

Silane modified magnetic nanoparticles as a novel adsorbent for determination of morphine at trace levels in human hair samples by high-performance liquid chromatography with diode array detection

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